Pain is divided into inflammatory pain, neuropathic pain, nociceptive pain, psychotic (psychogenic) pain, etc., depending on the cause. The inflammatory pain is a pain generated as going with inflammation caused by extracorporeal and nociceptive mechanical stimulation, heat stimulation, chemical stimulation, and the like. It is known that when an inflammatory pain occurs, not only inflammatory sites, but also inflammatory cytokines and cyclooxygenase existed in the spinal cord also play important roles. Neuropathic pain is a pathological pain caused by dysfunction of the peripheral or central nervous system itself. The psychotic pain is a pain generated due to an injury of a normal tissue or the application of a nociceptive stimulation which possibly causes an injury of a normal tissue, and is divided into bodily pain and visceral pain.
As a therapeutic agent for inflammatory pain, a cyclooxygenase (COX) inhibitor such as indomethacin, a cyclooxygenase II (COX-II) inhibitor such as celecoxib, a central analgesic such as tramadol, an analgesic-antipyretic agent such as paracetamol, and the like may be used. However, if the cyclooxygenase inhibitor is used for a prolonged period, as a side effect sometimes gastrointestinal disturbance may be caused, which is problematic. Additionally, as reported the cyclooxygenase II inhibitor may also cause gastric ulcer, and recently its side effects in heart circulation system, such as myocardial infarction, cerebral infarction and the like, also come as problem issues.
As a therapeutic agent for neuropathic pain, a papaverine-like analgesic such as morphine, an anticonvulsive drug such as gabapentin and pregabalin may be used, but it is known that along with the prolonged use time, it is sometimes necessary to increase the dosage and thus a side effect such as sedation may be caused. Currently there are no existing pharmaceutical agent which can be administrated safely without any side effect.
The patent literature 1 (WO2007/041863) described that ol 5-(((2-(6-amino)-9H-purin-9-yl)ethyl)amino)pentan-1-ol is capable of selectively inhibiting adenylate cyclase 1 and can be used for treating neuropathic pain and/or inflammatory pain. However, the patent literature 1 did provide neither a method suitable for preparing ol 5-(((2-(6-amino)-9H-purin-9-yl)ethyl)amino)pentan-1-ol for industrial application, nor a crystal form suitable for pharmaceutical preparation. Moreover, in respect of residual organic solvent in the final product, in different preparation and crystallization methods it is desirable to avoid the use of two or more types of organic solvents harmful to mammals, thereby reducing the adverse effect of residual organic solvent on the user.
For the polymorphic form of a medicament, different polymorphic forms may have different chemical and physical properties, including the melting point, chemical stability, apparent solubility, dissolution rate, optical and mechanical properties, vapor pressure, density and the like. These properties may directly or indirectly affect the processing or production of bulk pharmaceutical chemicals and formulations, and may also affect the stability, solubility and bioavailability of the formulations. Thus, the polymorphic form of the medicament is important for the quality, safety and efficacy of the pharmaceutical formulation. For ol 5-(((2-(6-amino)-9H-purin-9-yl)ethyl)amino)pentan-1-ol, the requirement thereof in the art is: having a polymorphic form which is suitable for industrial production and has excellent physicochemical properties.